Summary The long-term goal of this project is to understand the function of the actin-based motor, myosin VIIa, in the RPE. Loss of myosin VIIa function results in Usher syndrome type 1B, a combined deafness and blindness disorder. The current application is based on three new developments: (1) Evidence that, in the RPE, myosin VIIa may function in concert with microtubule motors; (2) Discovery of a link between myosin VIIa and the visual cycle; and (3) The establishment of live-cell imaging procedures for the study of RPE organelle transport by molecular motors. We propose to capitalize upon these new findings and developments by: (1) Studying the roles of myosin VIIa and microtubule motors in the transport of melanosomes, phagosomes, and lysosomes in the RPE; (2) Identifying and testing the function of microtubule-binding domain(s) of myosin VIIa; (3) Testing how myosin VIIa affects the visual cycle. The results of these studies will lead to a better understanding of critical cellular processes in the RPE cells, and provide a better basis for testing potential therapies for Usher 1B.